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Biomedical subjects

I Ferrer

Publications and source records attributed to I Ferrer.

At least 415 records · Page 23Linked to original sources
PubMedDate not supplied

[Neuronal death mechanisms in cerebral ischemia].

INTRODUCTION: Morphological and biochemical studies have shown an apoptotic component in neurons following either focal or global ischemia in adults, or hypoxia-ischemia during development. DEVELOPMENT: Different factors, including transcription factors, members of the Bcl-2 family, caspases and trophic factors, participate in the cascade of events leading to cell death. Transcription factor c-Jun is induced and expressed in the three models of ischemia as a non-specific response to the ischemic stress. The role played by the different members of the Bcl-2 family is not clear in cerebral ischemia. It is feasible that Bcl-2 expression is not sufficient to protect nerve cells from dying in those animals with physiological dotations of this protein. Yet Bcl-xS may have a role in ischemia-induced cell death following global ischemia in the adult or hypoxia-ischemia during development. Recent studies have also shown a similar putative role of caspase 1 and caspase 3 following cerebral ischemia. Finally, the ischemic insult is usually accompanied by modifications in the expression of neurotrophins and receptors. CONCLUSIONS: Brain-derived neurotrophic factor (BDNF) administration preserves nerve cells from dying following focal or global ischemia in adults, and hypoxia-ischemia during development. This positive effect is probably dependent on the cross-signaling between BDNF and its specific receptor TrkB. Cumulative evidence in experimental models indicates BDNF as a putative agent in the treatment of cerebral ischemia in humans.

Adult↗
PubMedDate not supplied

[Pathology of paraneoplastic syndromes of the central and peripheral nervous systems and muscle ].

INTRODUCTION AND DEVELOPMENT: The paraneoplastic neurological syndromes are alterations associated with neoplasias. However, they are not caused by metastases or complications such as infections, vascular disorders, metabolic or nutritional alterations or secondary effect of treatment. The paraneoplastic syndromes are often associated with the creation of autoantibodies against antigens produced by the neoplastia, but also may be against other cells or target molecules of the patient. Sometimes, especially with antibodies directed against cell membrane proteins, there is a close relationship between the antibody and the target organ, as for example antibodies against the acetylcholine receptor in myasthenia gravis. On other occasions, especially when the antigen is intracellular, the mechanism of the autoantibody reaction is not known. Finally, in a third group, the antibody associated with a particular paraneoplastic neurological alteration has not been identified. In this paper we describe the main paraneoplastic neurological pictures and known antibodies, including the molecular aspects and the neoplasias most frequently related to them.

Adult↗
PubMedDate not supplied

[Cell signaling in the epileptic hippocampus].

Cell signaling commanding death or survival in human epileptic hippocampus is difficult to trace because of the long interval between the beginning of symptoms and the sampling of damaged cerebral tissue for neuropathological examination. Intraperitoneal injection of the glutamate analogue kainic acid (KA) is a useful tool to analyze the effects of seizures and the excitotoxic damage in the rodent hippocampus. KA acts on NMDA and KA receptors, whereas it has little impact on AMPA receptors. Neurons of the hilus and CA3 neurons are primary targets of KA, although parvalbumin containing GABAergic neurons are less vulnerable than glutamatergic neurons. Immediate responses to KA are hsp 70 mRNA induction and HSP 70/72 protein expression, as well as c fos and c jun mRNA, and c Fos and c Jun protein expression in the hippocampus. Yet increased c Fos and c Jun expression is not a predictor of cell death or cell survival. In contrast, the tissular plasminogen activator (tPA) and the membrane Fas/Fas L signaling pathway probably have a role in facilitating cell death following KA injection. The involvement of other pathways remains controversial. Increased expression of the pro apoptotic Bax together with decreased Bcl 2 suggests Bax mediated apoptosis. Activation of the mitochondrial pathway includes leakage of citochrome c to the cytosol and activation of the caspase cascade leading to apoptosis. However, other studies have emphasized the limited expression of caspase 3, the main executioner of apoptosis, and the relevance of necrosis as the main form of cell death following KA excitotoxicity. Phosphorylation dependent activation of several kinases, including MAPK, p 38 and JNK/SAPK, and their substrates has been found in KA treated animals. Decreased CREBp expression is associated with cell death whereas increased ATF 2P and Elk 1P are associated with cell survival. Trophic factors probably do not play a significant role during the early stages of hippocanmpal damage but they are important in the remodeling of the granukle cells and the sprouting of mossy fibers to the molecular layer of the dentate gyrus. This abnormal regeneration, in turn, facilitates seizure recruitment and the chronic maintenance of convulsions.

Animals↗
PubMedDate not supplied

[Congenital insensitivity to pain with anhidrosis associated with congenital myasthenic syndrome].

INTRODUCTION: Congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV (HSAN IV) is a rare autosomal recessive disorder featuring recurrent fever episodes, inability to sweat, absent response to noxious stimuli, self mutilating behavior and mental retardation. It has been associated with mutations in the NTRK1 gene, located in 1q21-22 and encoding a high-affinity NGF receptor. CASE REPORT: An 8-year-old boy, the first son of consanguineous parents, presented with hypotonia, episodic hyperpyrexia and global developmental delay since the neonatal period. In addition to these signs, typical of CIPA, he displayed some other not previously described in this disease, such as facial dysmorphism, a severe swallowing disorder and a myogenic EMG pattern, that led to the initial suspicion of a muscle disorder. Molecular genetics studies uncovered a mutation c.C2011T in exon 15 of the NTRK1 gene. Genetic counselling was possible in the following pregnancy of the couple, where the female fetus was found to harbour the mutation in heterozygosity. The subsequent diagnosis of a congenital myasthenic syndrome in this sister led to neurophysiological re-evaluation of the probandus, in whom a myasthenic pattern of muscle activation was also found. CONCLUSIONS: A patient with CIPA and congenital myasthenic syndrome is described. CIPA must be the first diagnostic hypothesis when assessing a patient with insensitivity to pain, anhidrosis and self-mutilation. Given the rather homogeneous presentation of CIPA, the occurrence of atypical myopathic manifestations should raise the suspicion of a concurrent disorder. The present consanguineous kindred illustrates a rare instance of transmission of two mutated alleles giving rise to two unrelated, infrequent neurological syndromes.

Alleles↗
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[A study of senile plaques with a combined method in brains of patients suffering from Alzheimer's disease].

Combined immunocytochemistry to phosphorylated neurofilament epitopes and periodic-acid methenamine silver (PAM) were used in the study of senile plaques (SP) in 6 patients with Alzheimer disease. SP are categorized as diffuse, primitive, mature and burned-out. Amyloid deposits are found in all of them, which is loose in diffuse and primitive plaques, and condensed in mature and burned-out types. Dystrophic neurites are only found in primitive and mature plaques. Combined methods have also shown that apparently isolated dystrophic neurites in the neuropil are always associated to amyloid deposits. These features suggest that amyloid deposition is a primary event in SP formation.

Adult↗
PubMedDate not supplied

A Golgi study of cerebellar malformation in 13 trisomy.

The structure of cerebellar malformations in the brains of two infants with 13 trisomy has been studied by means of the Golgi method. Poorly organized cerebellar dysplasias (heterotaxias) are composed of Purkinje, Golgi and granule cells arranged and oriented in a disorderly fashion. The variable orientation and organization of the dendritic arbor of Purkinje cells within these cellular aggregates is supposed to be related to abnormal distribution of parallel fibers. Large ganglion cell heterotopias are not a homogeneous group, but two distinct types may be defined. First, Purkinje cell heterotopias which are located in the white matter of the cerebellum below the normally formed folia; these are composed of large neurons with arrested migration to the cortex. Secondly, multipolar cell heterotopias which are located in the deep white matter near the dentate and the roof nuclei, formed of neurons belonging to the deep cerebellar nuclei.

Abnormalities, Multiple↗
PubMedDate not supplied

Purkinje cells in degenerative diseases of the cerebellum and its connections: a Golgi study.

The cellular pathology of Purkinje cells in several degenerative diseases of the cerebellum and its connections was studied with the rapid Golgi method. Purkinje cells from a patient with Creutzfeldt-Jakob disease (case 1) showed decreased numbers of spiny branchlets. In a patient with a cystic infarct of the cerebellar white matter and chronic deafferentation of the cerebellar cortex (case 2) there was a striking increase in the density of spines on the primary dendrites. No abnormalities were observed in Purkinje cells from two patients with hereditary spinocerebellar degeneration (cases 3 and 4). Purkinje cells in two patients with olivopontocerebellar atrophy (OPCA) had severely reduced numbers of dendritic branches. Ballooned proximal axons were found in Purkinje cells with severely damaged dendrites (cases 5 and 6). In contrast to experimental olivary degeneration in laboratory animals, Purkinje cells from patients with OPCA did not have increased numbers of stubby spines in stout proximal dendrites but few spines with long pedicles were observed in the proximal segment of the primary dendrites and in the cellular body.

Adult↗
PubMedDate not supplied

Leucodystrophy with pigmented glial and scavenger cells (pigmentary type of orthochromatic leucodystrophy).

A 38-year-old man with progressive psychiatric disturbances, dysarthria, myoclonus, rigidity and terminal generalized seizures died 4 years after onset. At post-mortem, severe leucodystrophy of the centrum semi-ovale, corpus callosum and internal capsule was found. In the demyelinated areas, abundant mononuclear phagocytes were found filled with dark yellow or brown pigment granules, staining with PAS and Sudan black, autofluorescent in paraffin sections, and orthochromatic with toluidine blue in paraffin and frozen sections and positive with Fontana's silver method. Iron deposits were present in a few cells. Electron micrographs of a biopsy showed massive storage of lipofuscin and ceroid with fingerprint profiles in macrophages and, to a lesser degree, in astrocytes as well. Oligodendroglia were depleted in demyelinated areas but prominent in the subcortical regions and in small foci in the deep cerebral white matter; they contained intracytoplasmic inclusions with fingerprint profiles. From these morphological findings it is suggested that lipofuscin and ceroids are the lipopigments stored in the pigmentary type of orthochromatic leucodystrophy.

Adult↗